Background & objective: Sciatic nerve blocks under ultrasound guidance serve as fundamental procedures for lower limb anesthesia because they provide better safety and accuracy. The procedural outcome depends on sciatic nerve depth variations which become more significant when patients have high BMI or systemic comorbidities or musculoskeletal abnormalities. The research investigated sciatic nerve depth measurements in the popliteal fossa through ultrasound imaging while analyzing its connection to patient demographics and American Society of Anesthesiologists classifications and anthropometric measurements. Methodology: The research involved 90 adult patients who underwent lower limb surgery with 45 males and 45 females. Researchers recorded demographic information together with BMI measurements and thigh size and leg length data. The popliteal fossa sciatic nerve depth was measured through ultrasound examinations. The research team performed statistical tests that included Pearson correlation and multiple linear regression analysis and subgroup comparisons through gender, ASA grade, and BMI category. Results: The ultrasound measurements showed that female patients had deeper sciatic nerves than male patients (3.8 +/- 1.0 cm vs. 3.4 +/- 0.8 cm; P = 0.03). A positive relationship existed between BMI measurements and mid-thigh diameter dimensions when compared against nerve depth measurements in patients (r = 0.28, P = 0.007 and r = 0.21, P = 0.04 respectively). The independent predictors of increased sciatic nerve depth included BMI (beta = 0.06, P = 0.004), mid-thigh diameter (beta = 0.03, P = 0.010) and female gender (beta = 0.42, P = 0.008) and ASA Grade III (beta = 0.37, P = 0.030). The nerve depth increased progressively from normal weight patients (3.2 cm) to obese patients (4.1 cm) with statistical significance (P < 0.001). The study revealed anatomical variations in 57.8% of the patients. Conclusion: The depth of the sciatic nerve in the popliteal fossa shows a direct correlation with BMI and thigh diameter and gender and ASA classification. The results demonstrate why healthcare providers should perform customized preoperative assessments to maximize the effectiveness of ultrasound-guided blocks especially when treating patients with complex body structures or obesity.